title: Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers.
abstract: OBJECTIVE
  This exploratory study in healthy volunteers investigated the effect of single doses of oxycodone on gastrointestinal (GI) transit time and the degree to which a single dose of naloxone reverses the oxycodone-induced effect.
  
  
  METHODS
  Fifteen healthy male volunteers received: oxycodone 10 and2 0 mg, oxycodone/naloxone 10/5 and 20/10 mg (all as prolonged release tablets) and placebo. Each dose was radiolabelled and administered with a capsule containing radiolabelled resin (surrogate for GI contents).
  
  
  RESULTS
  Scintigraphic analysis showed that 20 mg oxycodone significantly increased colon arrival time (mean 7.19 vs 5.15 h for placebo, p = 0.0159). Mean colon arrival time for oxycodone/naloxone 20/10 mg (5.16 h) was similar to placebo, although the difference between oxycodone/naloxone 20/10 mg versus oxycodone 20 mg was not significant (p = 0.0653). Colonic geometric centre analysis showed a significant increase in mean time for the resin to reach the colon following oxycodone 10 and 20 mg compared with placebo (increases of 5.3 and 8.8 h). There was no significant effect of naloxone at the lower dose; however, oxycodone/naloxone 20/10 mg significantly reduced mean colonic transit time by 2.1 h (p = 0.0376).
  
  
  CONCLUSIONS
  A single dose of oxycodone 20 mg significantly prolonged GI transit time but this effect was reduced by co-administration of naloxone.
authors.affiliation: Mundipharma Research Ltd, Cambridge Science Park, Cambridge, UK. kevin.smith@mundipharma-rd.eu
authors.forename: Kevin
authors.initials: K
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Hopp
authors.forename: Gill
authors.initials: G
authors.lastname: Mundin
authors.forename: Simon
authors.initials: S
authors.lastname: Bond
authors.forename: Paul
authors.initials: P
authors.lastname: Bailey
authors.forename: Jo
authors.initials: J
authors.lastname: Woodward
authors.forename: Karuppan
authors.initials: K
authors.lastname: Palaniappan
authors.forename: Ann
authors.initials: A
authors.lastname: Church
authors.forename: Marie
authors.initials: M
authors.lastname: Limb
authors.forename: Alyson
authors.initials: A
authors.lastname: Connor
mesh_terms: D000328:Adult; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects*; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011877:Radionuclide Imaging / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009270:Naloxone; D010098:Oxycodone